Submissions for variant NM_001267550.2(TTN):c.14353G>A (p.Ala4785Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV004729208	SCV005333599	uncertain significance	not provided	2024-01-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss of function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005241024	SCV005887676	uncertain significance	not specified	2025-01-22	criteria provided, single submitter	clinical testing	Variant summary: TTN c.10621G>A (p.Ala3541Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 248198 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.10621G>A in individuals affected with Autosomal Recessive Titinopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3342448). Based on the evidence outlined above, the variant was classified as uncertain significance.