ClinVar Miner

Submissions for variant NM_002775.5(HTRA1):c.883G>A (p.Gly295Arg)

dbSNP: rs587776873
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001852016 SCV002266259 likely pathogenic not provided 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 295 of the HTRA1 protein (p.Gly295Arg). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects HTRA1 function (PMID: 31316458). 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 expected to disrupt HTRA1 protein function. ClinVar contains an entry for this variant (Variation ID: 30244). This missense change has been observed in individuals with autosomal dominant and recessive cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (PMID: 21115960, 28782182). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs587776873, gnomAD 0.002%).
GeneDx RCV001852016 SCV002526216 likely pathogenic not provided 2021-12-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect on trimerization and protease activity (Uemura et al., 2019); This variant is associated with the following publications: (PMID: 31589614, 32017060, 31316458, 21115960, 28782182)
OMIM RCV000023168 SCV000044459 pathogenic CARASIL syndrome 2010-11-30 no assertion criteria provided literature only
GeneReviews RCV000023168 SCV000189228 not provided CARASIL syndrome no assertion provided literature only

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