ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.12905C>A (p.Ser4302Tyr)

dbSNP: rs778808568
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000701275 SCV000830067 uncertain significance Spastic paraplegia 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 4302 of the SACS protein (p.Ser4302Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 578310). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SACS protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004702346 SCV005204226 uncertain significance not specified 2024-06-20 criteria provided, single submitter clinical testing Variant summary: SACS c.12905C>A (p.Ser4302Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.12905C>A in individuals affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 578310). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001274916 SCV001459469 uncertain significance Charlevoix-Saguenay spastic ataxia 2020-09-16 no assertion criteria provided clinical testing

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